rs10489885

chr1-88803823-G-A

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_006256.4(PKN2):c.1282-568G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0399 in 151,940 control chromosomes in the GnomAD database, including 278 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.040 (278 hom., cov: 32)
• Consequence: PKN2 NM_006256.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.598

Genes affected

PKN2 (HGNC:9406): (protein kinase N2) Enables RNA polymerase binding activity; histone deacetylase binding activity; and protein serine/threonine kinase activity. Involved in several processes, including apical junction assembly; positive regulation of cell cycle; and positive regulation of viral genome replication. Located in several cellular components, including cleavage furrow; cytoskeleton; and midbody. [provided by Alliance of Genome Resources, Apr 2022]

LOC124904214 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.88).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.102 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PKN2	NM_006256.4	c.1282-568G>A		intron_variant		ENST00000370521.8
LOC124904214	XR_007066211.1			downstream_gene_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PKN2	ENST00000370521.8	c.1282-568G>A		intron_variant		1	NM_006256.4	P1
PKN2	ENST00000370513.9	c.1282-1023G>A		intron_variant		1
PKN2	ENST00000316005.11	c.1282-568G>A		intron_variant		5
PKN2	ENST00000436111.1	c.440-568G>A		intron_variant		3

Frequencies

GnomAD3 genomes AF: 0.0398 AC: 6036 AN: 151822 Hom.: 273 Cov.: 32

Gnomad AFR AF: 0.105

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0384

Gnomad ASJ AF: 0.00664

Gnomad EAS AF: 0.0424

Gnomad SAS AF: 0.0704

Gnomad FIN AF: 0.000379

Gnomad MID AF: 0.00633

Gnomad NFE AF: 0.00721

Gnomad OTH AF: 0.0240

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.0399 AC: 6058 AN: 151940 Hom.: 278 Cov.: 32 AF XY: 0.0398 AC XY: 2952 AN XY: 74236

Gnomad4 AFR AF: 0.105

Gnomad4 AMR AF: 0.0382

Gnomad4 ASJ AF: 0.00664

Gnomad4 EAS AF: 0.0425

Gnomad4 SAS AF: 0.0700

Gnomad4 FIN AF: 0.000379

Gnomad4 NFE AF: 0.00721

Gnomad4 OTH AF: 0.0247

Alfa AF: 0.0219 Hom.: 30

Bravo AF: 0.0438

Asia WGS AF: 0.0650 AC: 224 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
Cadd	Benign	1.7
Dann	Benign	0.58
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs10489885; hg19: chr1-89269506;